The present invention belongs to the fields of pharmaceutical and organic chemistry, and provides an economical process for recovering a valuable byproduct in the synthesis of difluoronucleosides.
The difluoronucleosides were first disclosed by Hertel in U.S. Pat. Nos. 4,526,988 and 4,692,434, which are incorporated herein by reference. Hertel taught the synthesis of the difluoronucleosides, and showed that they are active as antivirals. Later, it was learned by Grindey and Hertel that the difluoronucleosides are valuable anticancer drugs, see European Patent Publication 0184365. Research on the difluoronucleosides continues intensively, and it is probable that at least one of them, 2'-deoxy-2',2'-difluorocytidine, will be approved for therapeutic use in cancer patients.
Hertel taught that the .beta.-configuration difluoronucleoside is the more important form, see column 3 of U.S. Pat. No. 4,526,988. Further research has shown that the .beta.-configuration compounds are difficultly obtainable in pure form, and that the available syntheses are likely to produce a mixture of the .alpha.- and .beta.-forms.
The difluoronucleosides are made up of a base moiety, which is easily and cheaply prepared, and a difluororibofuranose moiety, which is expensive. The present process provides a convenient route for recovering the difluoro sugar moiety from the o-configuration difluoronucleosides, in the form of an intermediate which is conveniently recycled.